The development of a predictive pharmacokinetic model for the disposition of a toxic agent will be of use in evaluating the effects of various dose levels. The purpose of the model is to estimate a priori the tissue levels to be expected from exposure to industrial chemicals as an aid in correlating the observed pathologies. Physiologically based pharmacokinetic models utilize readily available parameters, such as organ volumes and flows, to predict certain aspects of the drug distribution, and also as a basis for scaling animal results to humans. Questions pertaining to membrane permeabilities, binding, etc., for the specific neurotoxic agent, 2,5-hexanedione, and incorporation into physiological pharmacokinetic models, are to be studied. Labeled 2,5-hexanedione (administered ip) will be used in tissue distriubution studies as a basis for development of the pharmacokinetic model. Of special interest will be concentration levels in and around nerves and spinal cord, which should help in clarifying the ultimate cytotoxicity. Specifically, questions pertaining to a "dying back" phenomenon being responsible for the observed pathologies should be clarified. Extension of the pharmacokinetic model to include lung uptake from inhalational exposure will also be studied.